Hexanal → HCID 17972745, compound

Participants

Reaction Conditions

Reaction Steps

A solution of N-(4-bromo-2-fluorophenyl)-2,2-dimethylpropanamide (22.6 g, 82.5 mmol) in anhydrous tetrahydrofuran (410 mL) was placed under a nitrogen atmosphere, cooled in a dry ice-acetone bath, and stirred while butyllithium (83 mL of a 2.5M solution in hexanes, 207.5 mmol) was added dropwise by syringe pump over 2.5 hours. The resulting mixture was aged at −78° C. for 30 minutes and then treated with hexanal (25 mL, 208 mmol) added dropwise by syringe pump over 135 minutes. After stirring at −78° C. for an additional 70 minutes, the mixture was removed from the cooling bath, treated with aqueous 50% saturated NH4Cl, and the layers separated. The aqueous portion was extracted with EtOAc. The combined organics were washed with aqueous NaHCO3 and brine, dried over MgSO4, filtered, and concentrated under vacuum to an oil. The crude product was purified by flash chromatography on a Biotage 75 L KP-Sil column, eluting with 4:1 hexanes-EtOAc (25×400 mL fractions). Fractions 9–22 were combined and evaporated under vacuum to afford N-[2-fluoro-4-(1-hydroxyhexyl)phenyl]-2,2-dimethylpropanamide (18.5 g, 76%) as a clear oil.

Provenance & Evidence